Stroke is the fifth leading cause of death and the leading cause of chronic disability in the United States. Each year approximately 780,000 people suffer an acute ischemic stroke (AIS) in the United States at a cost of over $60 billion annually to the US health care system. Up to half of these strokes are due to thromboembolic occlusion of a large cerebral artery potentially accessible by catheter for endovascular treatment. Emergent large vessel occlusion (ELVO) AIS is particularly devastating and, due to the amount of thrombus burden in the arteries at the base of the brain in this disease, intravenous tPA is often insufficient to recanalize the cerebral arteries, reperfuse the brain tissue, and prevent irreversible infarction. In 2015 five randomized controlled clinical trials demonstrated the clinical superiority of catheter-based endovascular embolectomy to medical therapy alone in the first six hours after stroke onset. This has transformed the stroke community, with efforts to organize comprehensive stroke centers to treat ELVO patients rapidly along the lines of heart attack or major trauma treatment in the cardiology and trauma communities, respectively. Fewer than 10% of ischemic stroke patients receive treatment largely due to the narrow recommended time window for therapy within 3-6 hours of stroke onset. The basis for this recommendation is that the longer brain is deprived of blood flow, the more likely it is to infarct, and the more infracted brain there is, the more likely it is to hemorrhage after opening the occluded artery. Advances in neuroimaging are shifting the paradigm from ?time is brain? to ?physiology is brain?. Perfusion imaging (CT and MRI) and diffusion weighted MR imaging (DWI) now allow detection not only of infarcted brain but also of brain that is potentially salvageable if blood flow can be restored. MR DWI is the gold standard in medical imaging for identifying irreversibly infarcted brain (core infarct). Brain can progress from reversible but severe ischemia to irreversible infarction over the matter of minutes. Whereas current acute stroke diagnosis occurs by CT or MRI, treatment requires moving the patient to an X-ray angiography suite for endovascular therapy, leading to delays in care and variability in clinical outcomes. Current X-ray guided endovascular stroke treatment procedures have limitations that could be overcome using MRI guidance, including real-time tissue viability assessment and, in some cases, enhanced catheter navigation. We propose to develop the endovascular tools needed to treat patients safely and effectively whether in the strong magnetic field environment of MRI or the high ionizing radiation environment of X-ray angiography. Devices that are safe to use in the 3T MRI environment would allow patients to be treated in any standard clinical MRI scanner, thus allowing real- time assessment of brain viability during endovascular intervention. The strong magnetic field of the MRI scanner provides a unique opportunity to develop remote-controlled catheters that can navigate through the vasculature by creating magnetic forces on their tips. We have previously developed such magnetically assisted remote controlled (MARC) catheters for use in larger vessels of the body and neck; we now propose to develop smaller, more flexible versions for use in the vessels of the brain. Success in this project could transform the treatment of diseases like AIS that benefit from real-time physiologic tissue monitoring during therapy, thereby maximizing benefits and minimizing risks of treatment.

Public Health Relevance

Stroke is one of the leading causes of death and the leading cause of long-term disability for adults in the United States. Although emergent large vessel occlusion (ELVO) stroke is currently treated through the blood vessels under X-ray guidance, MRI is the gold standard for evaluating if brain tissue is alive and can be saved if blood flow is restored to it during a stroke. We propose to form a multidisciplinary, multi-institution, university and corporate consortium to develop and validate novel endovascular tools needed to treat patients safely and effectively whether in the strong magnetic field environment of MRI or the high ionizing radiation environment of x-ray angiography, allowing the stroke patient to be entirely diagnosed and treated in one location, saving time, optimizing brain tissue saved, and ultimately leading to improved clinical outcomes.

Agency
National Institute of Health (NIH)
Institute
National Institute of Biomedical Imaging and Bioengineering (NIBIB)
Type
Research Project (R01)
Project #
5R01EB012031-07
Application #
9881283
Study Section
Biomedical Imaging Technology Study Section (BMIT)
Program Officer
Wang, Shumin
Project Start
2011-08-01
Project End
2022-03-31
Budget Start
2020-04-01
Budget End
2021-03-31
Support Year
7
Fiscal Year
2020
Total Cost
Indirect Cost
Name
University of California San Francisco
Department
Radiation-Diagnostic/Oncology
Type
Schools of Medicine
DUNS #
094878337
City
San Francisco
State
CA
Country
United States
Zip Code
94118
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